6. Project Summary/Abstract This proposal is for the development of a fiber-optic based system for the detection and surveillance of early stage bladder cancer. The technology is based on Polarized Elastic Scattering Spectroscopy (PESS). Over 500,000 people in the US are afflicted with bladder cancer. Detection currently depends on visual examination by white light cystoscopy. This is generally performed when a patient presents with symptoms like hematuria or abnormal cells in the urine. This is followed by biopsy and surgical intervention. The recurrence rate for bladder cancer after surgery is an onerous 50-70%. This results in multiple repeat endoscopies and surgeries, with continued discomfort and stress to the patient. Bladder cancer is also the most expensive cancer, with an annual estimated cost in the US of $4B and a lifetime treatment cost for each surgical patient in the range of $100-200K. Early detection before the cancer reaches an invasive stage is often critical to long-term prognosis. The primary goals of this proposal are to determine the feasibility of using PESS for detecting early stage bladder cancer and developing PESS into a tool for optically guided interventions as well as a routine endoscopic screening tool for the doctor's office. Co-registration of a biopsy site with the site of spectroscopic measurement has been a consistent problem with optically and image-guided endoscopic and surgical interventions. To address this problem, a tool will be developed during this Phase 1 program that integrates a PESS fiber-optic probe with commercially-available biopsy forceps to ensure accurate correlation of histopathology with spectroscopic data. This optically-guided biopsy tool will be used in a 30-patient preliminary clinical study to acquire PESS spectra and histopathological assessments of samples biopsied from the same site. These data will be used to determine preliminary correlation between PESS spectral features and tissue histology for empirical classification of PESS spectra as indicative of normal urothelium, interstitial cystitis, low-grade bladder carcinoma, or high-grade bladder carcinoma. A successful Phase 1 outcome will lead to a broader multi-center Phase II clinical study, refined algorithms for tissue classification, and commercialization of the integrated optically-guided biopsy forceps. PESS has the potential to differentiate between normal and diseased tissues with sensitivity and specificity >90% using no indicator dyes, molecular markers, or other exogenous agents. Compared to imaging modalities such as NMR, CT and ultrasound, optically-guided PESS technology is simple, low cost, and easy to use with minimal training. PESS' ability to quickly detect lesions with high sensitivity and specificity can lead to fewer unnecessary tissue biopsies, earlier detection of recurrence, and reduced need for post-operative cystoscopic examinations, while reducing the cost of health care and improving patient outcomes and quality of life. OTI, with deep experience in optically- guided technology development, along with a world-class team of collaborators including Boston University, the Fraunhofer Institute, and Cook Urological, Inc. is uniquely equipped to successfully complete this program. 7. PUBLIC HEALTH RELEVANCE: Bladder cancer is the fifth most commonly diagnosed malignancy in the United States, and its high recurrence rate requires frequent post-operative visits for cystoscopic examination and surgery when new cancers are observed. Current clinical methods and practice are directed at surgically removing tumors identified visually or from biopsy of visually `suspicious' areas. If successful, the outcome of this grant will be a method of detecting bladder cancer before it is visible, allowing for earlier detection and treatment with fewer unnecessary tissue biopsies, a reduction in the need for post-operative follow-up and intervention, while reducing the cost of health care and improving patient outcomes and quality of life. [unreadable] [unreadable] [unreadable]